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DNA Could Be One of a Million Possible Genetic Molecules

Ryan F. Mandelbaum Nov 13, 2019. 9 comments

There could be a million different structures with the ability to store genetic information, according to a recent paper.

DNA stores the genetic information that describes all of Earth’s life, in the form of a twisted scaffold lined with a sequence composed of four data-encoding molecules. But is DNA the best way to store biological data for every purpose? What if there are better molecules for other purposes?

The new research points “toward there being large spaces of unexplored chemistry relevant to pharmacology and biochemistry and efforts to understand the origins of life,” according to the paper published in the Journal of Chemical Information and Modeling.

The researchers uncovered the rich variety of possible data storage molecules using a program called MOLGEN 5.0. They started by defining what a nucleic acid-like component should be made from, beginning with a “fuzzy” base molecular formula. They also defined what its structure should be: It needs a piece that another molecule reading the component can recognize as the data (in DNA, this is the A, T, C, and G, or nucleobase) as well as points to connect the recognizable unit to the scaffolding and to link each of those components into a larger molecule. Then, they used another program called Pipeline Pilot to generate new structures with the same chemical formulas to see what they might have missed. Finally, they compared the output to databases of molecules to see if any of their new molecules already existed, and used another computer program to exclude molecules that violated various chemistry restrictions.

No one actually produced these molecules. According to the paper, this work is “the first systematic attempt” to list, count, and describe the space of all nucleic acid-like molecules.

This team of scientists first simply explored molecules with the same chemical formula as, but different structure from, RNA—the single-stranded copies of DNA that the body actually uses as instructions for building proteins. Extending this study to more general chemical formulas generated an enormous list of unexplored possibilities for what genetic material might look like: 1,160,990 different structures.

“It is truly exciting to consider the potential for alternate genetic systems based on these analogous nucleosides—that these might possibly have emerged and evolved in different environments, perhaps even on other planets or moons within our solar system,” said study author Jay Goodwin, senior research fellow in chemistry at Emory University, said in a news release. “These alternate genetic systems might expand our conception of biology’s ‘central dogma’ into new evolutionary directions, in response [to] and robust to increasingly challenging environments here on Earth”

Considering these other possible genetic molecules could help scientists better understand the origin of RNA and DNA and why they look the way they do on Earth. It might also help synthetic biologists hoping to use DNA-like molecules as biological storage drives .

It’s exciting stuff. “This paper is a remarkably thorough analysis” of the field, George Church, professor of genetics at Harvard Medical School, told Gizmodo in an email. Now that such an analysis exists, “we might be surprised how quickly the community makes these and tests them for possibly utility.”

In other words, now that the list is out there, expect scientists to begin digging in and exploring whether any of these possible molecules have use in the real world.

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